Seventy-two percent of 86 major depressive patients with atypical features as defined by the DSM-IV and evaluated systematically were found to meet our criteria for bipolar 11 and related “soft” bipolar disorders; nearly 60% had antecedent cyclothymic or hyperthymic temperaments. The family history for bipolar disorder validated these clinical findings. Even if we limit the diagnosis of bipolar II to the official DSM-IV threshold of 4 days of hypomania, % of atypical depressives in our sample would meet this conservative threshold, a rate that is three times higher than the estimates of bipolarity among atypical depressives in the literature. By definition, mood reactivity was present in all patients, while interpersonal sensitivity occurred in 94%. Lifetime comorbidity rates were as follows: social phobia 30%, body dysmorphic disorder 42%, obsessive-compulsive disorder 20%, and panic disorder (agoraphobia) 64%. Both cluster A (anxious personality) and cluster B (., borderline and histrionic) personality disorders were highly prevalent. These data suggest that the “atypicality” of depression is favored by affective temperamental dysregulation and anxiety comorbidity, clinically manifesting in a mood disorder subtype that is preponderantly in the realm of bipolar II. In the present sample, only 28% were strictly unipolar and characterized by avoidant and social phobic features, without histrionic traits.